Comparing brain radiotherapy timing in lung cancer patients with ALK rearrangements

DURABLE: Delayed or Upfront Brain RAdiotherapy in Treatment naïve Lung Cancer Patients With Asymptomatic or Minimally Symptomatic Brain Metastases and rEarrangements

This study is testing whether a targeted lung cancer treatment called alectinib works better alone or with brain radiation for patients who have lung cancer with specific genetic changes and brain metastases.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hoosier Cancer Research Network (Academic / other)
• Drugs / interventions: alectinib, chemotherapy, immunotherapy, radiation
• Locations: 3 sites (Stanford, California and 2 other locations)
• Trial ID: NCT05987644 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of alectinib, a targeted therapy, in treating treatment-naïve lung cancer patients with asymptomatic or minimally symptomatic brain metastases and ALK rearrangements. The study consists of a Phase 1b portion where participants receive alectinib alone, followed by a Phase 2 portion that compares alectinib alone to a combination of alectinib and stereotactic radiosurgery (SRS). Each treatment cycle lasts 28 days, with a maximum of 25 cycles over two years. The goal is to determine the optimal timing for administering brain radiotherapy in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with Stage IV non-small cell lung cancer and confirmed ALK rearrangements who have at least one intracranial metastasis.

Not a fit: Patients with symptomatic brain metastases or those requiring surgical intervention may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could improve treatment outcomes for lung cancer patients with brain metastases by optimizing the timing of radiotherapy.

How similar studies have performed: Other studies have shown promising results with targeted therapies like alectinib in similar patient populations, indicating potential for success in this approach.

Eligibility criteria

General Inclusion Criteria:

Subject must meet all of the following applicable inclusion criteria to participate in this study:

1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. Age ≥ 18 years at the time of consent.
3. Fluent English skills with comprehensive/speaking skills equal to those of a native English speaker as assessed by the site investigator.
4. ECOG Performance Status of ≤ 2 within 14 days prior to registration.
5. Histological or cytological confirmation of Stage IV (per AJCC 8th edition) non-small cell lung cancer (NSCLC).
6. At least one intracranial metastasis on MRI imaging.
7. Confirmation of positive ALK rearrangement per local standard of care testing.
8. All subjects must have brain metastases and be either asymptomatic or minimally symptomatic per investigator discretion without plan for surgical intervention within 28 days of study start. Patients with neurological symptoms that are controlled with dose of corticosteroids or anti-epileptic medications are eligible. Patients with asymptomatic leptomeningeal disease may be eligible for trial providing they meet all other eligibility criteria.
9. Subjects must be planning on therapy with alectinib. Alectinib may have been started up to 8 weeks prior to registration.
10. Prior non-ALK directed therapy for metastatic disease is permitted. Patients who have received prior neoadjuvant or adjuvant chemotherapy, radiotherapy, immunotherapy (PD-1 or PD-L1 monoclonal antibodies) or chemoradiotherapy with curative intent for non-metastatic disease must have experienced a treatment-free interval of at least 3 months from registration since the last chemotherapy, radiotherapy, immunotherapy, or chemoradiotherapy cycle.
11. Documentation of consultation with a radiation oncologist confirming review and approval of the radiation therapy plan as outlined in Section 5.
12. Demonstrate adequate organ function as defined in the protocol. All screening labs to be obtained within 14 days prior to registration.
13. Females of childbearing potential must have a negative serum pregnancy test within 14 days prior to registration. See protocol for definition of childbearing potential.
14. Females of childbearing potential and males must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception as outlined in the protocol.
15. HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of registration are eligible for this trial.
16. Patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial.
17. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria:

Subjects meeting any of the criteria below may not participate in the study:

1. Active infection requiring systemic therapy.
2. Malabsorption syndrome or other condition that would interfere with enteral absorption
3. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
4. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per treating physician discretion, are not eligible for this trial.
5. Treatment with any investigational drug within 28 days prior to registration.
6. Acute viral, autoimmune, alcoholic, or other types of acute hepatitis.

Where this trial is running

Stanford, California and 2 other locations

• Stanford University — Stanford, California, United States (Recruiting)
• University of Colorado Cancer Center — Aurora, Colorado, United States (Recruiting)
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (Recruiting)

Study contacts

• Principal investigator: Joshua D Palmer, MD — The Ohio State University Comprehensive Cancer Center
• Study coordinator: Joshua D Palmer, MD

Conditions Lung Cancer; NSCLC; Brain Metastases